Degradation of most proteins in eukaryotic cells is through the ubiquition-proteasome system(UPS).Recently,it demonstrated that UPS regulates cell apoptosis and cardiac hypertrophy.The differences of UPS regulation lie in E3 ligases,which specifically recognize targets and direct the ubiquitination process.Recent evidence suggests that atrogin-1/muscle atrophy F-box(Mafbx) and muscle RING finger 1(MuRF1) may be critical mediators of the heart and muscle atrophy and hypertrophy.This review summarizes the possible relationship between UPS and cardiac dysfunction after myocardial infarction in order to inhibit cardiac dysfunction after myocardial infarction.

Carboxyl terminus of the HSP70-interacting protein (CHIP) is a co-chaperone of HSPs as well as an E3 ubiquitin ligase, and it is the connexin between heat shock proteins and ubiquitin-proteasome system. Recent research discovered that CHIP also possesses an intrinsic chaperone activity that enables it to recognize and bind nonnative proteins independently. CHIP regulates the HSPs expression and activity, and facilitates the client proteins ubiquitination and subsequent proteasome-dependent degradation. CHIP also inhibits apoptosis through MAPKs signaling pathways, and affects eNOS specific activity by means of the effects on Akt. Moreover, CHIP plays an important role in mitochondrial oxidative stress protection. With these above points, this paper reviews the function of CHIP in myocardial ischemia/reperfusion injury.

OBJECTIVE:To provide reference for the hospitals about emergency drug supply and pharmaceutical support in case of emergent events.METHODS:The pertinent literature both at home and abroad was retrieved and summarized analytically.RESULTS:The definition and the classification of emergent events were introduced,and the emergency drug supply and pharmaceutical support both at home and abroad in case of emergent event were introduced.CONCLUSIONS:Drugs are essential thing in medical aid in case of emergent events,and medical institutions should establish a scientific and practical drug supply system,and the pharmacists should bring their professional talents into full play by participating in medical aid in case of emergent event to ensure safe,effective and economic drug use.

Objective To explore the influence of proteasome inhibitor, MG-132 (N-benz0y1oxycarbonyl(Z)-Leu-Leuleucina1) on the expressions of carboxyl terminus of the Hsc70-interacting protein (CHIP) and heat shock protein 70 (HSP70) in ischemia reperfusion (I/R) rats and investigate the underlying mechanism of myocardial protection by the inhibitor. Methods Totally 54 adult SD rats were randomly divided into 3 groups, sham group (n=6), I/R group (n=24) and treatment group (I/R+T, n=24). The later 2 groups were further equally divided into 3 subgroups according different time of reperfusion. Left anterior descending (LAD) coronary artery was ligated for 30 min and then released for 2 h or 24 h or 7 d in different subgroups. Five minutes before reperfusion, MG-132 at dose of 0.75 mg/kg was given intravenously in I/R+T group,but I/R group and sham group were given the same volume of normal saline. The levels of CHIP and HSP70 at mRNA and protein level were detected by real-time PCR and Western blotting respectively. The correlation between CHIP and HSP70 expression was analyzed. Results Compared with I/R groups, the mRNA levels of CHIP and HSP70 were significantly increased in I/R+T groups (P

OBJECTIVE:To provide references for drug administrator in coping with the challenge of drug shortage and the promotion of rational drug use. METHODS: With American Society of Hospital Pharmacists Guidelines on Managing Drug Shortages as references,the feasible management strategies for drug shortage in China were put forward based on the reality of our country and our experience in the practice of drug shortage management. RESULTS & CONCLUSIONS: It is advisable to draw experiences from U.S. Food and Drug Administration to tackle the problem of the shortage of essential drugs through the co-efforts of Ministry of Public Health,State Food and Drug Administration and Stage Development and Reform Committee and develop contingency planning strategy in health care organization to deal with the shortages of certain drugs and reduce potential clinical safety hazard induced by drug shortages.

Objective To investigate the pregnancy outcome of frozen-thawed embryos transfer in different endometrial progesterone preparation time.Methods From January to December 2012,pregnant outcome of 1 103 frozen-thawed embryo transfer cycles using artificial periodic endometrial preparation were studied retrospectively in Reproductive Medical Center of Henan Provincial People's Hospital.It was divided into 4 groups:group 3-3 (n =543,3 days after endometrial progesterone preparation and transfer D3 embryo),group 4-3(n =330,4 days after endometrial progesterone preparation and transfer D3 embryo),group 5-5 (n =150,5 days after endometrial progesterone preparation and transfer D5 blastula),group 6-5 (n =80,6 days after endometrial progesterone preparation and transfer D5 blastula).The rate of implantation,pregnancy,ectopic pregnancy,multiple pregnancy,and first trimester abortion were compared among those groups.Results (1) With the different endometrial progesterone preparation methods and transfer D3 embryos,implantation rate [group 3-3:39.9％ (429/1 074) ; group 4-3:44.1％ (286/648)],pregnancy rate [group 3-3:56.0％ (304/543) ; group 4-3:59.4％ (196/330)],ectopic pregnancy rate [group 3-3:3.3％ (10/304) ; group 4-3:2.6％ (5/196)],multiple pregnancy rate [group 3-3:38.5％ (117/304) ; group 4-3:43.4％ (85/196)]and early abortion rate[group 3-3:13.5％ (41/304); group 4-3:13.3％ (26/196)] had no significant differences between group 3-3 and group 4-3 (all P ＞ 0.05).(2) With the different endometrial progesterone preparation methods and transfer D5 blastocysts,implantation rate [group 5-5:64.7％ (191/295) ; group 6-5:69.4％ (100/144)],pregnancy rate [group 5-5:80.7％ (121/150) ; group 6-5:78.8％ (63/80)],ectopic pregnancy rate [group 5-5:2.5％ (3/121) ; group 6-5:0],multiple pregnancy rate[group 5-5:55.4％ (67/121) ; group 6-5:46.3％ (37/80)] and early abortion rate[group 5-5:5.8％ (7/121); group 6-5:7.9％ (5/63)].However,there were no significantly differences between group 5-5 and group 6-5 (all P ＞ 0.05).Conclusions The two different progesterone transformed endometrial methods can obtain satisfactory clinical outcome with D3 embryo or D5 blastocysts transfor.It is convenient to clinical and laboratory work arrangements.

Objective To study the effect of estradiol supplementation during the luteal phase on mouse endometrial expression of leukaemia inhibitory factor and pinopodes in controlled ovarian stimulation cycles.Methods Female mice were randomly divided into four groups:group A[controlled ovarian stimulation(COS)group],group B(COS group with progesterone for luteal-phase-support),group C(COS group with progesterone and estradiol for luteal-phase-support),and group D of natural cycle group.Pinopodes were investigated by scanning electronic microscopy(SEM)in the uterine endometrium of pregnant mice on pregnancy days(pa)3-5.LEukaemia inhibitory factor(LIF)protein Was determined by immunohistochemistry in the uterine endometrium of pregnant mice on pd 3-5.Results (1)In groups B,C,and D,there were small developed pinopodes in the endometrial surface of pregnant mouse on day 3;there were large fully developed pinopodes in endometrial surface,which Was smooth with well defined borders resembling a mushroom on day 4.The regressing pinopodes were observed on day 5.In group A,there were small developed pinopodes in endometrial surface of pregnant mouse on day 3.The regressing pinopodes were seen on day 4.(2)In the pregnant mice of groups C and D,the level of LIF protein on days 3-5 ( 138.5±20. 3,143.1±19. 0) was significantly higher than group A ( 103. 2 ± 5.0, P < 0. 05 ), and strong immunostaining of LIF protein was found on day 4 of gestation. In group B, the level of LIF protein on days 3-5 ( 123.5±10. 8)was significantly higher than group A (P <0. 05), but significantly lower than groups C and D ( P <0. 05 ). Strong immunostaining of LIF protein was found on day 4 of gestation. In group A, weak immunostaining of LIF protein peaked on day 3 of gestation. In groups B, C, and D, the level of LIF protein on day 4 was significantly higher than group A on day 3 ( F = 55.76, P < 0. 01 ). Conclusions Estradiol supplementation during the luteal phase can improve the expression of LIF and pinopodes in mouse endometrium in controlled ovarian stimulation cycles and redress the harmful effect on implantation window by COS. Therefore, estradiol supplementation can improve the endometrial receptivity.

Objective To evaluate the role of transvaginal color Doppler ultrasound measurements of endometrial thickness,endometrium and subendometrial blood distribution patterns and flow index in predicting endometrial receptivity and pregnancy outcome of freezing embryo transfer(FET).Methods 468 cycles FET were analysed retrospectively.Endometrial thickness,endometrium and subendometrial blood distribution patterns,pulsatility index (PI),resistance index (RI),systolic /diastolic ratio (S/D) of endometrial and subendometrial blood flows with transvaginal ultrasonography were measured on the day of progesterone initiation.Based on the clinical pregnancy or not,patients were divided into two groups.The comparison of these indicators were carried out between pregnant group and non pregnant group.Results The endometrium and subendometrial blood distribution patterns had statistical difference between the two groups(P ＜0.05),the clinical pregnancy rate of Ⅰ,Ⅱ,Ⅲ blood distribution patterns were 31.0％,62.5％,79.0％ respectively.In the pregnancy group,the S/D,PI,and RI of endometrium were significantly lower than those in the nonpregnant group (P ＜ 0.05),and there was no significant difference between the pregnant group and nonpregnant group in endometrial thickness(P ＞0.05).Conclusions Endometrium and subendometrial blood distribution patterns and flow index measured with transvaginal color Doppler ultrasound could assess endometrial receptivity and guide the time selecting of FET transplantation.

Objective To study ovarian development in vitrificatiou of embryos born mice and expression of growth differentiation factor 9 ( GDF-9 ) in its.MethodsThe vitrification recovery embryos (vitrified-embryo group) and fresh embryos (fresh-embryo group) were transplanted into pseudopregnant mice,respectively.The female offspring mice in two groups were sacrificcd on the 3rd,7th,14th,21st,28th and 60th day after birth,the ovarian tissues were taken,6 mice in each time point of each group.The ovarian development was observed by HE staining,the expression of GDF-9 mRNA and protein at each time point of two groups were detected by reverse transcription(RT)-PCR and western blot.ResultsHE staining showed that no abnormal ovarian development was observed in offsprings at two groups.On the 3rd,7th,14th,21st,28th and 60th day after birth,the expression of GDF-9 mRNA in vitrified-embryo group were 0.14 ± 0.07,0.42±0.16,1.00±0.24,1.59±0.28,2.05 ±0.32 and 2.23 ±0.21,respectively,which in fresh-embryo group were 0.13 ±0.06,0.45 ±0.18,1.00 ±0.21,1.56 ±0.26,2.01 0.37 and 2.26 ±0.23,respectively,there was no statistical difference between two groups ( P ＞ 0.05 ) ; the expression of GDF-9 protein in vitrified-embryo group were 0.040 ± 0.030,0.120 ± 0.060,0.170 ± 0.030,0.250 ± 0.040,0.320± 0.060 and 0.330 ± 0.010,respectively,which in fresh-embryo group were 0.030 ± 0.020,0.110 ± 0.040,0.150 ± 0.010,0.210 ± 0.020,0.360 ± 0.070 and 0.350 ± 0.030,respectively,there was no statistical difference between two groups ( P ＞ 0.05 ).Conclusion The ovarian morphology in vitrification of embryos born mice and expression of GDF-9 in ovary has no any obvious change.

Objective To discuss the surgical management of von Hippel Lindau(VHL) syn drome.Methods The clinical data of four VHL patients who were clinically diagnosed from March1999 to October 2006 were reviewed.The first patient was a 56 year old man with the chief complaintof hypodynamia and low serum glucose as 2.37 mmol/L.CT scan showed three masses in the the leftkidney.He had a history of cerebral haemangioblastoma ten years before.The second case was a 57 year old woman with the chief complaint of lumbago in the left side.CT scan showed masses in theleft kidney,adrenal gland and panerease.The third case was a 39 year old woman with the chief com plaint of an accident mass in the left adrenal gland.She had the history of cerebellar hemangioblastoma9 years before,spinal hemangioblastoma resection 7 years before.The fourth case was a 41-year oldwoman,she was found brain tumors and cured by gamma radiation abalation.Bilateral renal masseswere found by B ultrasound one month later,CT scan showed four masses in the both kidneys,leftadrenal gland and pancreas.Results All 4 cases underwent surgical approach.The first case under went radical nephrectomy which pathological report was PEComa of kidney.The blood glucose wasnormal one week later.The second case underwent resection of the left adrenal gland,kidney,pancre atic body and tail and spleen.Pathological report was clear cell carcinoma,islet cell tumor and adrenal cyst.Three months later she was found spinal hemangioblastoma and refused treatment.The thirdcase underwent adrenalectomy in the left side and pathologieal report was adrenal pheoehromocytoma.There was not tumor reeurrenee during 2 years' follow up.The nephrectomy and adrenalectomy wasperformed for the last ease whose pathological report was clear celt carcinoma and pheochromoeytoma.Three weeks later,tumor enueleating of the right kidney was undertaken; the result was clear cellcancer.During the follow up for one year there was no relapse of tumor.Conclusions For VHL ac companied with multiple organ tumors,surgery resection is the proper approaeh when tumors of centralnervous system is large.Different approaches could be taken to deal with multiple tumors of VHL such aswatchful waiting,nephron sparing surgery.